Project 3: Menopause Aging, body fat distribution and cardiometabolic disease risk factors in menopausal African women Abstract Mid-life sub-Saharan African (SSA) females, particularly those living in urban areas, have a high prevalence of obesity and related cardiometabolic diseases (CMD). Furthermore, the prevalence of obesity in females across Africa and in other low and middle income countries is much higher than is observed in males. The reason for the high prevalence of obesity and its comorbidities is usually ascribed to poor lifestyle choices. However, data that has largely been collected in high income countries show that obesity and cardiovascular risk increase during menopause. It is therefore possible that in SSA women the menopause transition and its associated hormonal changes may contribute to the etiology of CMD within this population. Unfortunately, very few studies have investigated the contribution of the menopause transition to CVD risk in SSA women. A large observational study conducted on mid-life women in Soweto, South Africa has confirmed the high prevalence of obesity and higher blood pressure and lipid levels in post-menopausal compared to pre-menopausal females. However, this was a cross-sectional study and no longitudinal studies on the relationship between menopause and CMD risk factors have been conducted in SSA females. The aims of this study are therefore as follows: 1. To determine if the levels of specific CMD risk factors (i.e. lipids, glucose, insulin, blood pressure and carotid intima media thickness (cIMT) increase across the menopause transition in women resident in South Africa (3 sites: Soweto, Agincourt and Dikgale), Kenya, Ghana and Burkina Faso 2. To determine if BMI and body fat distribution, as measured using waist and hip circumference and visceral and abdominal subcutaneous fat thickness, increase across the menopause transition in women and correlate with changes in CMD risk factors 3. To determine if changes in sex hormone levels across the menopause transition correlate with changes in CMD risk factors and anthropometric variables 4. To determine if epigenetic changes in candidate genes related to sex hormone production and function are correlated with changes in the levels of sex hormones, CMD risk factors and anthropometric variables in women 5. To determine through the use of Mendelian Randomization whether sex hormones are modulators of BMI, body fat distribution and CMD risk factors This study will be the first large scale longitudinal analysis of changes in CMD risk factors and DNA methylation across the menopause transition in SSA women. It will test the hypothesis that hormonal and epigenetic changes during the menopause are drivers of obesity and CMD risk and will provide valuable information on the etiology of CMD in SSA women. The study will also highlight possible interventions for CMD in this population.